This is a proposal to investigate the properties of a series of 110 hypervariable loci in 11 defined human populations. The overall objective of the research is to improve our understanding of the biology of hypervariable loci. Hypervariable loci in non-transcribed, transcribed and translated regions will be compared to test the hypothesis that, because of natural selection, intrapopulation variance is reduced in coding regions. Variation in allele sizes will be compared in disease-causing trinucleotide systems versus trinucleotide systems that do not cause disease. It is hypothesized that the former will have higher mutation rates than the latter. Measures of interpopulation genetic variance will be evaluated to search for the possible effects of natural selection (in particular, balancing vs. directional or disruptive selection). Mutation rates will be measured and compared for each class of hypervariable loci (di-, tri-, and tetranucleotides), using family data. Frequency distributions of these loci will be examined to determine whether there are functional constraints on allele size.